I have established an independent clinical and translational research program in oncology, with a specific focus in lung cancer. My research has already led to the identification of promising treatment strategies and new predictive biomarkers, changed aspects of clinical trial design, and advanced numerous basic science discoveries into the clinic. Despite this success, time constraints on myself and other physician scientists are slowing the translation of biologic discoveries to the clinic, which in turn hampers the training of additional investigators. In the coming years, I will have the opportunity to make my greatest contributions yet to the field and the next generation of cancer researchers by addressing such timely and critical areas as: large-scale tumor genomic analysis; application of molecularly targeted therapies to resected early-stage lung cancer; repurposing of existing medications as cancer therapies to save resources and expedite drug development; combining immunotherapy and ionizing radiation to heighten lung cancer cure rates; and expanding clinical trial eligibility to augment study accrual, generalizability, and completion rates. The proposed K24 program will supplement and enhance my ongoing and planned research. It will provide me the training and experience to advance my career toward my stated long-term goals, while simultaneously allowing me to guide numerous trainees along their own professional trajectories. The career development, research, and mentoring supported by this award will contribute to my long-term goals: (1) Lead a major cancer research program that will advance the field of oncology at basic science, clinical, and population levels; (2) Improve the diagnosis, treatment, and outcomes of patients with lung cancer and other malignancies; and (3) Develop a new generation of clinical investigators armed with the knowledge and skill sets to conduct high-quality patient- oriented research in oncology. The Specific Aims of the proposal are: (1) Continue and enhance my career development as a leader in oncology patient-oriented research. I will (a) Participate in formal mentoring and leadership training programs locally; (b) Apply for the year-long American Society of Clinical Oncology (ASCO) Leadership Development Program; (c) Continue my current institutional research leadership positions; and (d) Interact with advisers locally and at other institutions. (2) Conduct independent research to improve cancer treatment and outcomes. Studies will (a) Determine the prevalence and prognostic impact of a prior cancer diagnosis in early-stage and locally advanced lung cancer; (b) Determine if molecularly targeted, personalized treatment of resected early-stage lung cancer improves survival; (c) Determine whether the anti-fungal agent itraconazole impacts angiogenesis and developmental pathways when repurposed as a novel lung cancer treatment; (d) Determine whether combining immunotherapy with standard chemoradiation for locally advanced lung cancer improves survival; and (e) Determine optimal administration and preliminary efficacy of a novel DNA damaging strategy in a biomarker-selected population. (3) Mentor trainees to become independent clinical investigators. This will be achieved through (a) Direct involvement in independent research projects; (b) Practical and didactic research training; (c) Exposure to biomarker development, implementation, and interpretation; and (d) Participation in a novel peer-based mentoring program. By accelerating critical patient-oriented research, training, and mentoring in oncology, the K24 will expand and enhance the field, ultimately leading to the development of new cancer treatments and investigators.